Enhanced Fat Grafting With A Nanofiber-hydrogel Composite: A Biomimetic Approach To Soft Tissue Reconstruction

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PURPOSE: Autologous fat grafting (AFG) is a mainstay in the management of soft tissue defects. Yet, efficacy is often limited by poor and unpredictable survival. Graft failure is inadequate vascularization and lack of an adherent substrate for integrin-dependent survival. We hypothesized that a nanofiber-hydrogel composite (NHC) designed to mimic the native extracellular matrix could address both of these challenges and markedly enhance graft survival. METHODS: An injectable NHC was formulated from hyaluronic acid hydrogel and poly(ε-caprolactone) (PCL) nanofiber fragments. To test its efficacy, emulsified groin fat from Lewis rats was combined with the NHC in various ratios. Five experimental groups were established and injected subcutaneously (500-600 L) into rats: (A) 100% NHC, (B) 75% NHC-25% fat, (C) 50% NHC-50% fat, (D) 25% NHC-75% fat, and (E) 100% fat. Grafts were harvested at multiple time points up to 90 days post-operation (POD 90). Analysis included volumetric assessment of graft retention and immunohistochemical staining for viable adipocytes (Perilipin), apoptosis (Caspase-3), and vascular structures (RECA-1/αSMA). RESULTS: The 50% NHC-50% fat group demonstrated significantly superior outcomes compared to all other fat-containing groups. At POD 90, the 50/50 grafts maintained approximately 40% of their initial volume, whereas the 100% fat grafts retained less than 20%. Histological analysis revealed that 50/50 grafts preserved their adipose tissue structure, while 100% fat grafts showed significant degradation. The 50/50 grafts sustained a high percentage of Perilipin-positive viable adipocytes from POD 30 to POD 90 (30% vs 38% respectively, p=0.2), in stark contrast to the 100% Fat group, which experienced significant adipocyte loss over the same period (4% at POD 30 vs 0.5% at POD 90, p<0.05). Furthermore, the 50/50 grafts exhibited minimal Caspase-3 activity, while the 100% Fat and 25% NHC-75% fat groups showed strong evidence of apoptosis. Critically, the 50/50 grafts developed a robust vascular network at POD 90, showing a significantly higher degree of vascularization (2.3% vs 1.8 at POD30, p<0.05) than all other groups throughout the study. CONCLUSION: The co-administration of fat and NHC in a 1:1 ratio creates a supportive microenvironment that significantly enhances fat graft survival. This optimal balance between a biomimetic scaffold and native tissue fragments promotes rapid vascularization, which in turn reduces ischemia-induced apoptosis and improves long-term volume retention. The NHC-fat composite can be described as a hybrid graft able to overcome the key limitations of traditional autologous fat grafting. *Source: https://ps-rc.org/meeting/Program/2026/AS42.cgi*

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